GLP1-1RAs improve walking distance and reduce amputation in people with type 2 diabetes and peripheral artery disease: A systematic review and meta-analysis of randomised controlled trials and cohort studies.

Giugliano D, Longo M, Di Martino N, Scappaticcio L, Caruso P, Bellastella G, Maiorino MI, Esposito K

Diabetes, obesity & metabolism8 Jan 2026Cited by 2 (Europe PMC)

PMID41508745DOI10.1111/dom.70454PepBankPUB-41508745

Publisher page PubMedAsk about this study

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study9

2 results from studies that gave the peptide. 2 results from people.

01HumanSystematic reviewEfficacy outcome
In people with type 2 diabetes and peripheral artery disease, subgroup analysis linked tirzepatide to a 55% lower risk of lower extremity amputation.
In plain wordsIn people with type 2 diabetes and peripheral artery disease, tirzepatide was linked to lower leg amputation risk than placebo or other glucose-lowering drugs.
Peptide
Tirzepatide
Outcome
DecreaseLower extremity amputation risk reduction
Study
n: not reported in source
Comparator
Placebo or other glucose-lowering drugs
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Measurements
risk reduction
55%
tirzepatide, lower extremity amputation
Source sentences
Summary
Subgroup analyses showed a significant difference (p < 0.001) between GLP-1RA therapies, with the strongest associations with LEA reduction for tirzepatide and semaglutide (55% and 54% risk reduction, respectively
2 context sentences(design, population, supporting numbers)
Summary · context
We included studies enrolling adults with type 2 diabetes and PAD, comparing GLP-1RAs against placebo or other glucose-lowering drugs.
Summary · context
We included seven studies (3 RCTs, 4 cohorts) enrolling 107 092 participants.
Report a problemFND-4150874501
02HumanSystematic reviewEfficacy outcome
In adults with type 2 diabetes and peripheral artery disease, semaglutide was associated with a 54% lower risk of lower extremity amputation in the subgroup analysis.
In plain wordsIn adults with type 2 diabetes and leg artery disease, semaglutide use was linked to fewer leg amputations.
Peptide
Semaglutide
Outcome
DecreaseLower extremity amputation risk reduction (semaglutide subgroup)
Study
n: not reported in source
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
Dose not stated
Measurements
Risk reduction
54%
semaglutide, LEA
Source sentences
Summary
Subgroup analyses showed a significant difference (p < 0.001) between GLP-1RA therapies, with the strongest associations with LEA reduction for tirzepatide and semaglutide (55% and 54% risk reduction, respectively)
1 context sentence(design, population, supporting numbers)
Summary · context
We included studies enrolling adults with type 2 diabetes and PAD, comparing GLP-1RAs against placebo or other glucose-lowering drugs.
Report a problemFND-4150874507

Studies that did not test the peptide alone7

In this study, the peptide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking the peptide.

03HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes and peripheral artery disease, pooled cohort studies of GLP-1 receptor agonists (including semaglutide) linked treatment to a lower risk of lower extremity amputation.
In plain wordsIn cohort studies of GLP-1 drugs as a class, including semaglutide, use was linked to fewer leg amputations.
Peptide
Semaglutide
Outcome
DecreaseLower extremity amputation risk (pooled GLP-1RA cohort studies)
Study
n = 104,292
Outcome group
Cardiovascular events · Cardiovascular
Measurements
Risk ratio
0.53 RR
LEA, GLP-1RAs
Source sentences
Summary
The meta-analysis of four cohort studies with 104 292 participants showed that GLP-1RAs reduced the risk of LEA (RR = 0.53, 95% CI 0.39-0.73, p 2 = 85.96%), totally related to one study, and very low certainty of evidence.
1 context sentence(design, population, supporting numbers)
Summary · context
We included studies enrolling adults with type 2 diabetes and PAD, comparing GLP-1RAs against placebo or other glucose-lowering drugs.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4150874505
04HumanNot a test of Liraglutide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes and peripheral artery disease, pooled cohort studies of GLP-1 receptor agonists (including liraglutide) linked treatment to a lower risk of lower extremity amputation.
In plain wordsIn cohort studies of GLP-1 drugs as a class, including liraglutide, use was linked to fewer leg amputations.
Peptide
Liraglutide
Outcome
DecreaseLower extremity amputation risk (pooled GLP-1RA cohort studies)
Study
n = 104,292
Outcome group
Cardiovascular events · Cardiovascular
Measurements
Risk ratio
0.53 RR
LEA, GLP-1RAs
Source sentences
Summary
The meta-analysis of four cohort studies with 104 292 participants showed that GLP-1RAs reduced the risk of LEA (RR = 0.53, 95% CI 0.39-0.73, p 2 = 85.96%), totally related to one study, and very low certainty of evidence.
1 context sentence(design, population, supporting numbers)
Summary · context
We included studies enrolling adults with type 2 diabetes and PAD, comparing GLP-1RAs against placebo or other glucose-lowering drugs.
In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Liraglutide.
Report a problemFND-4150874506
05HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes and peripheral artery disease, pooled randomized trials of exenatide or semaglutide showed no significant difference from placebo in major adverse limb events or amputation.
In plain wordsIn adults with diabetes and leg artery disease, pooled exenatide or semaglutide trials showed no clear difference from placebo in limb events or amputation.
Peptide
Semaglutide
Outcome
No significant changeMALE or LEA incidence (pooled exenatide or semaglutide RCTs)
Study
n = 3,592
Comparator
Placebo
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
In the additional meta-analysis of two RCTs with 3592 participants, the incidence of MALE or LEA did not differ significantly between patients receiving exenatide or semaglutide and those receiving placebo.
1 context sentence(design, population, supporting numbers)
Summary · context
We included studies enrolling adults with type 2 diabetes and PAD, comparing GLP-1RAs against placebo or other glucose-lowering drugs.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4150874504
06HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes and peripheral artery disease, pooled randomized trials of liraglutide or semaglutide showed improved walking distance.
In plain wordsIn adults with type 2 diabetes and artery disease in the legs, pooled trials of liraglutide or semaglutide showed longer walking distance.
Peptide
Semaglutide
Outcome
IncreaseWalking distance (pooled liraglutide or semaglutide RCTs)
Study
n = 847
Outcome group
Exercise and physical function · Cardiovascular
Measurements
Hazard ratio
1.1 ratio
walking distance, liraglutide or semaglutide
Source sentences
Summary
The meta-analysis of two RCTs with 847 participants demonstrated a significant improvement in walking distance with liraglutide or semaglutide (HR = 1.10, 95% CI 1.05-1.15, p 2 = 0.0%) and moderate certainty of evidence.
1 context sentence(design, population, supporting numbers)
Summary · context
We included studies enrolling adults with type 2 diabetes and PAD, comparing GLP-1RAs against placebo or other glucose-lowering drugs.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4150874502
07HumanNot a test of Liraglutide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes and peripheral artery disease, pooled randomized trials of liraglutide or semaglutide showed improved walking distance.
In plain wordsIn adults with type 2 diabetes and artery disease in the legs, pooled trials of liraglutide or semaglutide showed longer walking distance.
Peptide
Liraglutide
Outcome
IncreaseWalking distance (pooled liraglutide or semaglutide RCTs)
Study
n = 847
Outcome group
Exercise and physical function · Cardiovascular
Measurements
Hazard ratio
1.1 ratio
walking distance, liraglutide or semaglutide
Source sentences
Summary
The meta-analysis of two RCTs with 847 participants demonstrated a significant improvement in walking distance with liraglutide or semaglutide (HR = 1.10, 95% CI 1.05-1.15, p 2 = 0.0%) and moderate certainty of evidence.
1 context sentence(design, population, supporting numbers)
Summary · context
We included studies enrolling adults with type 2 diabetes and PAD, comparing GLP-1RAs against placebo or other glucose-lowering drugs.
In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Liraglutide.
Report a problemFND-4150874503
08HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes and peripheral artery disease, pooled GLP-1 receptor agonists (including semaglutide) showed no difference in amputation outcome when patients with diabetic foot ulcers at baseline were excluded.
In plain wordsIn pooled studies of GLP-1 drugs as a class, including semaglutide, leaving out people with foot ulcers did not change the amputation result.
Peptide
Semaglutide
Outcome
No significant changeLower extremity amputation excluding patients with diabetic foot ulcers (pooled GLP-1RAs)
Study
n: not reported in source
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
there was no difference in the LEA outcome excluding from the analysis patients with type 2 diabetes and diabetic foot ulcers at baseline
1 context sentence(design, population, supporting numbers)
Summary · context
We included studies enrolling adults with type 2 diabetes and PAD, comparing GLP-1RAs against placebo or other glucose-lowering drugs.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Report a problemFND-4150874508
09HumanNot a test of Liraglutide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes and peripheral artery disease, pooled GLP-1 receptor agonists (including liraglutide) showed no difference in amputation outcome when patients with diabetic foot ulcers at baseline were excluded.
In plain wordsIn pooled studies of GLP-1 drugs as a class, including liraglutide, leaving out people with foot ulcers did not change the amputation result.
Peptide
Liraglutide
Outcome
No significant changeLower extremity amputation excluding patients with diabetic foot ulcers (pooled GLP-1RAs)
Study
n: not reported in source
Outcome group
Cardiovascular events · Cardiovascular
Source sentences
Summary
there was no difference in the LEA outcome excluding from the analysis patients with type 2 diabetes and diabetic foot ulcers at baseline
1 context sentence(design, population, supporting numbers)
Summary · context
We included studies enrolling adults with type 2 diabetes and PAD, comparing GLP-1RAs against placebo or other glucose-lowering drugs.
In this study, Liraglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Liraglutide.
Report a problemFND-4150874509

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Versions 4 to 39Current
28 Oct 2026, 02:04 UTC
The same notice was added 36 times, first on 9 Oct 2026, 19:08 UTC. The status did not change between them.
Study results updated
Versions 2 to 3
9 Oct 2026, 03:07 UTC
The same notice was added 2 times, first on 9 Oct 2026, 03:06 UTC. The status did not change between them.
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:05 UTC
First added · source update from Europe PMC

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GLP1-1RAs improve walking distance and reduce amputation in people with type 2 diabetes and peripheral artery disease: A systematic review and meta-analysis of randomised controlled trials and cohort studies.

Summary

Results from this study9

Studies that did not test the peptide alone7

Version history

Subjects

Publication types

MeSH terms

Keywords